Salmonella enterica serovar Typhimurium (Salmonella Typhimurium) is one of the most common causes of enterocolitis in humans. Pathogenesis of this facultative intracellular pathogen is dependent on the ability to invade non-phagocytic cells, such as those found in the intestinal epithelium. Invasion is dependent on a Type 3 Secretion System (T3SS1), which is used to translocate a set of bacterial effector proteins into the host cell. Following internalization, intracellular Salmonella survive and replicate within a modified phagosome, the Salmonella-containing vacuole (SCV). In some cell types, particularly epithelial cells Salmonella can also replicate in the cytosol, although this does not occur in macrophages or other phagocytic cells. A second type III system (T3SS2), which is induced intracellularly, is associated with biogenesis of the SCV and with intravacuolar survival/replication. We are currently using both mouse and human macrophage model systems to dissect the roles of T3SS1 and T3SS2 in Salmonella-host cell interactions. We are also studying the expression of virulence genes in vitro.